Electrophoresis control system with wide dynamic range

ABSTRACT

The invention provides an electrophoresis system which separates charged chemical substances by means of applying an electrical potential across a buffer solution which includes those chemical substances. The system of the invention includes a power supply and control system which has a wide dynamic range of constant voltage, current and power which may be supplied, and is therefore particularly suited to the needs of the electrophoresis system. In the invention, the power supply includes a flyback topology and a control system which allows an operator to specify a wide range of constant voltage, current or power supply requirements for the electrophoresis system.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to electrophoresis systems. More specifically,this invention relates to an electrophoresis system which makes use of apower supply and control system of particular utility forelectrophoresis systems.

2. Description of Related Art

Electrophoresis is a process for separating chemical substances from oneanother by means of their differential molecular weights. The chemicalsubstances may be naturally charged, or a charge may be applied to themprior to electrophoresis. An electric potential is applied to themixture for a fixed time period, during which the lighter molecules willmove more quickly. At the end of the period, the lighter molecules willhave moved farther than the heavier molecules. Thus, one application ofthis process is to determine relative proportions of chemical substancesin a mixture.

One problem which has arisen in the art is the use and control of apower supply which has a sufficient dynamic range for electrophoresis.This problem is particularly acute in electrophoresis of DNA fragmentsand other bioactive and/or biochemical substances, or in electrophoresisof other chemicals which are to be separated in a gel. The gel commonlyhas a negative temperature coefficient, so an increase in current causesthe gel to heat up and to draw more current. Moreover, a widely varyingrange of chemicals to be separated, as may be common in electrophoresisof DNA fragments, may require widely varying voltage, current or powerrequirements.

Prior art electrophoresis systems have attempted to solve this problemby control circuitry for limiting the output of the power supply.However, while this solution will allow the electrophoresis system tooperate, it is not as effective or as efficient as if the power supplyitself had wide dynamic range, for each of supplied voltage, current andpower.

Another problem which has arisen in the art is that prior art powersupplies may be large, bulky and very heavy. This causes inconveniencein placing and using the electrophoresis system in a laboratoryenvironment. The circuitry of the present invention offers a size andweight advantage over prior art power supply and control systems.

SUMMARY OF THE INVENTION

The invention provides an electrophoresis system which separates chargedchemical substances by means of applying an electrical potential acrossa buffer solution which includes those chemical substances. The systemof the invention includes a power supply and control system which has awide dynamic range of constant voltage, current and power which may besupplied, and is therefore particularly suited to the needs of theelectrophoresis system. In the invention, the power supply includes aflyback topology and a control system which allows an operator tospecify a wide range of constant voltage, current or power supplyrequirements for the electrophoresis system. The circuitry for the powersupply and control system is particularly compact and affords a size andweight advantage over prior art systems.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram of an embodiment of the invention.

FIG. 2 is a circuit diagram of the power supply and control systemelement of an embodiment of the invention.

FIG. 3 is a drawing of a set of operator controls in an embodiment ofthe invention.

FIG. 4 is a circuit diagram of a feedback control section of anembodiment of the invention.

FIG. 5 is a circuit diagram of a display control section of anembodiment of the invention.

DESCRIPTION OF THE PREFERRED EMBODIMENT

The invention may be used together with several differentelectrophoresis systems which are not disclosed in detail herein Itwould be clear to one of ordinary skill in the art, after perusal of thespecification, drawings and claims herein, that coupling of thecircuitry disclosed herein to an electrophoresis system of common designwould be a straightforward task and would not require undueexperimentation. Accordingly, a more detailed description is notincluded herein.

FIG. 1 is a block diagram of an embodiment of the invention. Anelectrophoresis system 101 has a power supply and control system 102which supplies power for the electrophoresis process. In theelectrophoresis system 101, a mixture of chemical substances to beseparated is embedded in a gel 103 having an anode 104 and a cathode 105coupled to the power supply and control system 102. In a preferredembodiment, the gel 103 may be soaked in a radioactive probe and anultraviolet light 106 may be used to illuminate a DNA band 107 which hasbeen separated by the electrophoresis process. A more detaileddescription of the electrophoresis process and apparatus for conductingthe process may be found in "Electrophoresis: Theory, Techniques andBiochemical and Clinical Applications" (2d. ed.), by Anthony T. Andrews,published by Oxford University Press (New York, NY) in 1986, herebyincorporated by reference as if fully set forth herein.

Power Supply and Control System

FIG. 2 is a circuit diagram of the power supply and control system 102of an embodiment of the invention. The power supply and control system102 has a main input terminal 201 for accepting AC input power from anexternal source (not shown) and a main output terminal 202 forgenerating output power for the electrophoresis system 101. In apreferred embodiment, feedback and operator controls (see FIGS. 3-5)control the operation of the power supply and control system 102.

The main input terminal 201 is coupled to an input 203 of a primaryrectifier 204 by means of an EMI filter (not shown). The EMI filterprotects the external source from electromagnetic interference which maybe generated by the power supply and control system 102, as is wellknown in the art. In a preferred embodiment, the EMI filter may comprisepart number FN 322-6/05 made by Schaffner EMC, Inc. (Union, NJ). In apreferred embodiment, the primary rectifier 204 may comprise a set ofcapacitors 205 such as part number LP681M200C4P3 made by Aerovox(Glasgow, KY), and a set of diodes 206 such as part number PB66 made byDiodes, Inc. (Chatsworth, CA), configured as a full-wave or half-wavebridge rectifier, the structure of which is well known in the art.

An output 207 of the primary rectifier 204 is coupled to a power input208 of a solid-state switch 209. In a preferred embodiment, thesolid-state switch 209 may comprise a pair of 900 volt, 4 amp, MOSFETtransistors 210 coupled in parallel, such as part number IXTP4N90 madeby IXYS (San Jose, CA).

A control input 211 of the solid-state switch 209 is coupled to anoutput 212 of a main control circuit 213. In a preferred embodiment, themain control circuit 213 may comprise a 55 KHz pulse-width modulator (asset by a timing RC circuit, as is well known in the art) such as partnumber SG3524B made by Silicon General (Garden Grove, CA), arranged in acurrent mode control configuration, the structure of which is well knownin the art, to achieve stability throughout a wide dynamic range. Themain control circuit 213 generates a control signal whose duty factordepends upon its own inputs, as disclosed herein.

A power output 214 of the solid-state switch 209 is coupled to an input215 of a current-sense transformer 216, which generates a signalindicative of current. In a preferred embodiment, the current-sensetransformer 216 may comprise part number PE-51688 made by PulseEngineering (San Diego, CA). An output 217 of the current-sensetransformer 216 is coupled to a first input 218 of the main controlcircuit 213 (pin 4 of a preferred part, for primary current limitation).

The power output 214 of the solid-state switch 209 is also coupled to aprimary coil 219 of a transformer 220. In a preferred embodiment, thetransformer 220 may comprise a high-frequency flyback topology ferritetransformer with the primary coil 219 having 32 turns, a set of foursecondary coils 221 each having 65 turns and wound opposite to theprimary coil 219, and a total air gap of about 30 thousandths of aninch.

The four secondary coils 221 of the transformer 220 are configured tocarry a maximum of about 500 volts each, and are coupled to a set ofinputs 222 of a secondary rectifier 223, and the voltages are summed ata set of capacitors 224 of the secondary rectifier 223, such as partnumber 684MSR630K made by Illinois Capacitor (Lincolnwood, IL). In apreferred embodiment, the secondary rectifier 223 may also comprise aset of diodes 225 such as part number MUR180E made by Motorola (Phoenix,AZ).

An output 226 of the secondary rectifier 223 is coupled to the mainoutput terminal 202.

Voltage and Current Feedback

The main output terminal 202 also comprises a signal indicating measuredvoltage, and is coupled to a first input 227 of an error amplifier 228.A second input 229 of the error amplifier 228 accepts a control voltagefrom a control voltage terminal 230 (see FIG. 4). The error amplifier228 thus compares the measured voltage with the control voltage. In apreferred embodiment, the error amplifier 228 may comprise anoperational amplifier ("op-amp") arranged in an amplifier configuration,the structure of which is well known in the art, such as part numberLM358 made by National Semiconductor (Santa Clara, CA).

An output 231 of the error amplifier 228 is coupled to an input 232 of afirst opto-coupler 233. In a preferred embodiment, the firstopto-coupler 233 may comprise a combination of an LED 234 and aphototransistor 235, as is well known in the art, such as part numberH11AV2A made by Motorola. An output 236 of the first opto-coupler 233 iscoupled to a second input 237 of the main control circuit 213 (pin 5 ofa preferred part).

The main output terminal 202 is coupled to the electrophoresis system101, which imposes an electrical load. As disclosed herein, because thegel 103 commonly has a negative temperature coefficient, an increase incurrent causes the gel 103 to heat up and causes the electrophoresissystem 101 to draw more current.

A current sensor 238 measures a load current of the electrophoresissystem 101 and generates a signal indicating measured current. In apreferred embodiment, the current sensor 238 may comprise a set ofresistors arranged in series so as to measure current by the voltagedrop across the resistors, as is well known in the art.

An i-sense-2 output 239 of the current sensor 238 is coupled to anegative input 240 of a load detection amplifier 241. A positive input242 of the load detection amplifier 241 is coupled to a 5 mA fixedsource 243 indicating 5 mA current. In a preferred embodiment, the loaddetection amplifier 241 may comprise an op-amp arranged in an amplifierconfiguration, the structure of which is well known in the art, such aspart number LM358 made by National Semiconductor.

The i-sense-2 output 239 is also coupled to a positive input 244 of ashort-circuit detection amplifier 245. A negative input 246 of theshort-circuit detection amplifier 245 is coupled to a 75 mA fixed source247 indicating 75 mA current. In a preferred embodiment, theshort-circuit detection amplifier 245 may comprise an op-amp 248arranged in an amplifier configuration, the structure of which is wellknown in the art, such as part number LM358 made by NationalSemiconductor, coupled in series with a latch 249 such as part number74HC74 made by Motorola.

An output 250 of the load detection amplifier 241 is coupled to awire-OR node 251 by means of a first wire-OR diode 252, and an output253 of the short-circuit detection amplifier 245 is coupled to thewire-OR node 251 by means of a second wire-OR diode 254. The wire-ORnode 251 thus comprises an inhibit signal for the main control circuit213, and is coupled to an input 255 of a second opto-coupler 256.

In a preferred embodiment, the second opto-coupler 256 may comprise acombination of an LED 257 and a phototransistor 258, as is well known inthe art, such as part number H11AV2A made by Motorola. An output 259 ofthe second opto-coupler 256 is coupled to a third input 260 of the maincontrol circuit 213 (pin 9 of a preferred part, for inhibiting pulsegeneration).

Front-Panel Operator Controls

FIG. 3 is a drawing of a set of front-panel operator controls 301 in anembodiment of the invention. In a preferred embodiment, the operatorcontrols 301 may comprise the following controls and indicators:

A power switch 302 for turning the power supply on and off, having an"on" position and an "off" position.

A digital display 303. In a preferred embodiment, the digital display303 may comprise a four-digit LED display, the structure of which iswell known in the art.

A display select button 304 for selecting among display based onvoltage, current or power, and a set of indicators comprising a voltageindicator 305, a current indicator 306, and a power indicator 307. In apreferred embodiment, these indicators may be visual indicatorscomprising LED lamps.

An output short-circuit indicator 308. In a preferred embodiment, thisindicator may be a visual indicator comprising an LED lamp.

A set-point button 309 for selecting and deselecting a set-point, and aset-point indicator 310 for indicating when a set-point is selected. Ina preferred embodiment, the set-point indicator 310 may be a visualindicator comprising an LED lamp.

A set of adjustment controls comprising a voltage control 311, a currentcontrol 312 and a power control 313, for adjusting the desired voltage,current, and power respectively, each having a maximum-value indicatorfor voltage maximum 314, current maximum 315 or power maximum 316respectively, for indicating when a maximum value has been selected. Ina preferred embodiment, these maximum-value indicators may each be avisual indicator comprising an LED lamp.

A start button 317 for starting the power supply.

Effect of Feedback Controls

FIG. 4 is a circuit diagram of a feedback control section of anembodiment of the invention.

The operator controls 301 are coupled to a current control output 401, avoltage control output 402 and a power control output 403.

The current control output 401 is coupled to a first input 404 of acurrent differential amplifier 405. A second input 406 of the currentdifferential amplifier 405 is coupled to the i-sense-2 output 239 of thecurrent sensor 238.

The current differential amplifier 405 compares the load current of theelectrophoresis system 101 with the desired current set by the operatorby means of the current control 312. In a preferred embodiment, thecurrent differential amplifier 405 may comprise a set of two op-amps 407and 408 arranged in an amplifier configuration for positive swing only,the structure of which is well known in the art, such as part numbersLM301A and LM358 respectively, made by National Semiconductor.

An output 409 of the current differential amplifier 405 is coupled to aninput 410 of a current nonlinear amplifier 411. The current nonlinearamplifier 411 comprises an amplifier op-amp 412 coupled in an amplifierfeedback configuration with an amplifier transistor 413 coupled betweena negative input 414 and an output 415 of the amplifier op-amp 412. In apreferred embodiment, the amplifier op-amp 412 may comprise part numberLM358 made by National Semiconductor and the amplifier transistor 413may comprise part number 2N4220 made by Motorola.

An output 416 of the current nonlinear amplifier 411 is coupled to afirst summing input 417 of a summing amplifier 418.

The voltage control output 402 is coupled to a second summing input 419of the summing amplifier 418.

The power control output 403 is coupled to a first input 420 of a powerdifferential amplifier 421. A second input 422 of the power differentialamplifier 421 is coupled to a calculated power output 423 of themultiplier 502 (see FIG. 2) which calculates a product of measuredcurrent and measured voltage.

The power differential amplifier 421 compares the measured power of theelectrophoresis system 101 with the desired power set by the operator bymeans of the power control 313. In a preferred embodiment, the powerdifferential amplifier 421 may comprise a set of two op-amps 424 and 425arranged in an amplifier configuration for positive swing only, in likemanner as the current differential amplifier 405, such as part numbersLM301A and LM358 respectively, made by National Semiconductor.

An output 426 of the power differential amplifier 421 is coupled to aninput 427 of a power nonlinear amplifier 428. In a preferred embodiment,the power nonlinear amplifier 428 comprises an op-amp 429 and atransistor 430 configured in like manner as the current nonlinearamplifier 411.

An output 431 of the power nonlinear amplifier 428 is coupled to a thirdsumming input 432 of the summing amplifier 418.

In a preferred embodiment, the summing amplifier 418 may comprise asumming node 433 which is coupled to the first summing input 417, thesecond summing input 419 and the third summing input 432. The summingnode 433 is coupled to an input 434 of an op-amp 435 configured in anamplifier configuration, the structure of which is well known in theart, such as part number LM358 made by National Semiconductor.

An output 436 of the summing amplifier 418 is coupled to an input 437 ofan invertor 438. In a preferred embodiment, the invertor 438 maycomprise an op-amp configured in an inverting configuration, thestructure of which is well known in the art, such as part number LM358made by National Semiconductor.

An output 439 of the invertor 438 is coupled to the control voltageterminal 230.

Effect of Display Controls

FIG. 5 is a circuit diagram of a display control section of anembodiment of the invention.

A voltage input 501 of a multiplier 502 (see FIG. 2) is coupled to themain output terminal 202, indicating measured voltage. A current input503 of the multiplier 502 is coupled to the i-sense-2 output 239,indicating measured current. In a preferred embodiment, the multiplier502 may comprise an analog multiplier such as part number AD534JD madeby Analog Devices (Norwood, MA).

The calculated power output 423 of the multiplier 502 is coupled to afirst power input 504 of a normal/set switch 505, indicating measuredpower. A first voltage input 506 of the normal/set switch 505 is coupledto the main output terminal 202, indicating measured voltage. A firstcurrent input 507 of the normal/set switch 505 is coupled to ani-sense-1 output 508 of the current sensor 238, indicating measuredcurrent. In a preferred embodiment, the i-sense-1 output 508 and thei-sense-2 output 239 differ because they have differing voltage levelsfor the same indicated current.

The voltage control output 402 is coupled to a second voltage input 509of the normal/set switch 505. The current control output 401 is coupledto a second current input 510 of the normal/set switch 505. The powercontrol output 403 is coupled to a second power input 511 of thenormal/set switch 505.

The set-point button 309 is coupled to a control input 512 of thenormal/set switch 505 by means of a one-shot logic element 513,comprising a set-point latch 514 and a timeout element 515 configured toset the set-point latch 514 when the set-point button 309 is pressed andto reset the set-point latch 514 after a fixed period of time, as wouldbe clear to those of ordinary skill in the art. The normal/set switch505 selects between its first and second voltage, current and powerinputs respectively. In a preferred embodiment, the normal/set switch505 may comprise a multiplexor such as part number 4HC4053 made byMotorola.

A set of three outputs 516 of the normal/set switch 505, for voltage,current and power respectively, are coupled to a set of three inputs 517respectively of a display select mux 518. The display select mux 518selects among its voltage, current and power inputs. In a preferredembodiment, the display select mux 518 may comprise a shift register519, such as part number 74HC194 made by Motorola, for indicating whichone of voltage, current or power is selected, and a set of three analogswitches 520, such as part number 74HC4066 made by Motorola, each ofwhich is controlled by an output 521 of the shift register 519. Thedisplay select button 304 is coupled to a control input 522 of the shiftregister 519.

An output 523 of the display select mux 518 is coupled to the digitaldisplay 303 by means of a display driver 524. In a preferred embodiment,the display driver 524 may comprise an A/D converter and a displaydriver combined in one circuit, the structure of which is well known inthe art, such as part number ADD3701CCN made by National Semiconductor.

The circuitry for the power supply and control system 102 which has beendescribed above is particularly compact and affords a size and weightadvantage over prior art systems.

While preferred embodiments are disclosed herein, many variations arepossible which remain within the concept and scope of the invention, andthese variations would become clear to one of ordinary skill in the artafter perusal of the specification, drawings and claims herein.

We claim:
 1. An electrophoresis system for separating charged chemicalsubstances, comprisingmeans for applying an electrical potential to amixture of said charged chemical substances; first means for generatinga first control signal indicating constant voltage, constant current, orconstant power supply; second means for generating a second controlsignal indicating a choice of level of supply; third means forgenerating a constant level of supply of said electrical potential asindicated by said first control signal and second control signal,comprising a flyback transformer having a characteristic frequencyexceeding about 20 kilohertz and having at least one primary winding andat least one secondary winding with opposite polarity and having aferrite core with an air gap.
 2. An electrophoresis system as in claim1, wherein said third means for generating weighs less than about 6pounds.
 3. An electrophoresis system as in claim 1, wherein saidtransformer comprises a plurality of secondary windings having oppositepolarity from said primary winding and coupled to diode rectifiers, saiddiode rectifiers being coupled in series.
 4. An electrophoresis systemas in claim 1, wherein said third means for generating comprisesa switchcoupled to said transformer and coupled to an input power source; acircuit coupled to a control input of said switch and providing acontrol signal, whereby said switch causes said power source and saidtransformer to be coupled in accordance with said control signal; and afeedback circuit coupling an output of said third means for generatingto said circuit.
 5. An electrophoresis system as in claim 4, whereinsaid circuit is arranged in a current mode control configuration.
 6. Anelectrophoresis system as in claim 4, wherein said feedback circuitcomprises at least one second circuit coupled to a signal indicating asensed supplied electrical level, said second circuit comprising atransistor coupled between an input and an output of an amplifier.
 7. Anelectrophoresis system as in claim 6, wherein said supplied electricallevel is voltage, current, or power.
 8. An electrophoresis system as inclaim 6, comprising a plurality of said second circuits coupled to asumming circuit.